A latent form of persistent infection can be established in susceptible mice inoculated with defective Friend virus (i.e., spleen focus-forming virus (SFFV)) purified free from standard helper virus. The overall objective of the proposed research is to identify the hemopoietic site(s) of SFFV persistence, to investigate SFFV's ability to alter the frequency and function of puripotential stem cells (CFU-S) and erythroid progenitors, and to identify both virus- and host-controlled events which either contribute to or retard the development of Friend leukemia. To probe for SFFV-induced alteration in host hemopoiesis as a marker for preleukemic change, I shall employ cell transplantation techniques for CFU-S and in vitro cultures able to detect and quantify erythroid progenitor cells which are either erythropoietin dependent or independent (i.e., transformed). SFFV+ animals will be continuously monitored for the emergence of a population of hemopoietic cells which are able to be rejected by unimmunized, lethally irradiated syngeneic recipients. Since silica pretreatment may abrogate this rejection, I shall attempt to maintain and expand this population of SFFV+ preleukemic cells via serial bone marrow cell transplantation. Cells will be used to prepare anti-SFFV antisera. I shall also at regular intervals inoculate SFFV+ cells into syngeneic newborn mice to determine if these cells are able to grow as a transplantable erythroleukemia and determine if persistently infected mice, when lethally irradiated and reconstituted with normal hemopoietic donor cells, provide a leukemic (i.e., SFFV+) microenvironment which is able to induce a leukemia of donor cell origin. I shall probe for effector cells (using microcytotoxicity techniques) capable of anti-leukemogenic activity. Cells will be harvested from the lymphoid tissues of preleukemic SFFV+ mice. Such cells may play a significant role in determining the latency of this disease.